Browsing by Subject "RECURRENCE"

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  • Raisanen, Sari; Hogue, Carol J. R.; Laine, Katariina; Kramer, Michael R.; Gissler, Mika; Heinonen, Seppo (2018)
    ObjectiveTo examine the effect of pregnancy history on the risk of stillbirth. MethodsIn a population-based cross-sectional study, data were reviewed from all women aged at least 20years with singleton pregnancies in Finland between 2000 and 2010. The primary outcomestillbirthwas defined as fetal death after 22 gestational weeks or death of a fetus weighing at least 500g. ResultsAmong 604047 singleton pregnancies, the prevalence of stillbirth was 3.17 per 1000 deliveries. Prevalence was lowest for multiparous women without previous pregnancy loss after adjusting for major pregnancy complications associated with stillbirth (placenta previa, placental abruption, and pre-eclampsia) and other confounders. Relative to these women, stillbirth prevalence was higher among multiparous women with previous spontaneous abortion and/or stillbirth (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.05-1.36), nulliparous women with no previous pregnancy loss (aOR 1.23, 95% CI 1.10-1.38), and nulliparous women with prior spontaneous abortion (aOR 1.43, 95% CI 1.18-1.74). ConclusionPrevious pregnancy loss was found to be an independent risk factor for stillbirth, irrespective of the number of prior deliveries. Spontaneous abortion assessed as a part of pregnancy history was found to be an independent risk factor for stillbirth.
  • Mattila, Kalle E.; Laajala, Teemu D.; Tornberg, Sara V.; Kilpeläinen, Tuomas P.; Vainio, Paula; Ettala, Otto; Bostrom, Peter J.; Nisen, Harry; Elo, Laura L.; Jaakkola, Panu M. (2021)
    After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4-8.6) and 5.4 years (4.0-7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 +/- 0.029 and 0.836 +/- 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 +/- 0.035 and 0.848 +/- 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.
  • Eriksson, M.; Joensuu, H. (2021)
  • Heervä, Eetu; Väliaho, Vesa; Salminen, Tapio; Nieminen, Lasse; Carpelan, Anu; Kurki, Samu; Sundström, Jari; Huhtinen, Heikki; Rantala, Arto; Carpen, Olli; Minn, Heikki; Österlund, Pia; Ålgars, Annika; Ristamäki, Raija (2020)
  • Alhede, Christina; Lauridsen, Trine K.; Johannessen, Arne; Dixen, Ulrik; Jensen, Jan S.; Raatikainen, Pekka; Hindricks, Gerhard; Walfridsson, Haakan; Kongstad, Ole; Pehrson, Steen; Englund, Anders; Hartikainen, Juha; Hansen, Peter S.; Nielsen, Jens C.; Jons, Christian (2017)
    Background: Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods: Patients with paroxysmal AF (N = 260) enrolled in the MANTRA PAF trial were treated with AAD (N = 132) or CA (N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results: Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion: AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. (C) 2017 Elsevier B.V. All rights reserved.
  • Virkkula, P.; Penttilä, E.; Vento, S. I.; Myller, J.; Koskinen, A.; Hammaren-Malmi, S.; Laulajainen-Hongisto, A.; Hytönen, M.; Lilja, M.; Numminen, J.; Sillanpää, S.; Sahlman, J.; Toppila-Salmi, S. (2020)
    Background: Developing tools to identify chronic rhinosinusitis with nasal polyps (CRSwNP) patients requiring surgical treatment would help clinicians treat patients more effectively. The aim of this retrospective cross-sectional study was to identify cut-off values for eosinophil percentage, nasal polyps (NP), and Lund-Mackay (LM) scores that may predict the need for surgical treatment in Finnish CRSwNP patients. Methods: Data of CRSwNP patients (N = 378) undergoing consultation for ESS in 2001-19 were used. Data was collected from patient records and Lund-Mackay scores were determined from sinus computed tomography scans. The percentage of eosinophils was microscopically evaluated from the polyp samples available (n = 81). Associations were analyzed by Mann Whitney U test, and cut-off values by the area under the receiver operating characteristic curve (AUROC). Results: ESS was performed to 293 (77.5%) of patients. Polyp eosinophilia was associated significantly with ESS (p = 0.001), whereas peripheral blood eosinophil count, LM- score and endoscopic NP- score were not (p > 0.05). AUROC values (95% CI) for detecting those needing ESS were for polyp eosinophilia 0.71 (0.60-0.83), p = 0.001, for LM score 0.59 (0.50-0.67), p = 0.054; for NP score 0.56 (0.48-0.64), p = 0.17, and for blood eosinophil count 0.68 (0.46-0.90), p = 0.08. With the threshold value of polyp eosinophilia (>25%), the sensitivity and specificity were optimal for detecting the group needing ESS from the group not undergoing ESS. The cut-off value of blood eosinophil count (>0.26 x 10(9)/L) had relatively good, yet statistically insignificant (underpowered), predictive potential. Moderate cut-off values were found for endoscopic LM score (>= 14/24) and NP score (>= 4/8). Conclusions: Polyp eosinophilia (>25%) predicted ESS among Finnish hospital-level CRSwNP patients. A future challenge would be to find less invasive and cost-effective clinical factors predicting uncontrolled CRSwNP.
  • Gunnarsson, Ulf; Strigård, Karin; Edin, Sofia; Gkekas, Ioannis; Mustonen, Harri; Kaprio, Tuomas; Böckelman, Camilla; Hagström, Jaana; Palmqvist, Richard; Haglund, Caj (2020)
    Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities.
  • Söderholm, John J.; Socada, J. Lumikukka; Rosenström, Tom; Ekelund, Jesper; Isometsä, Erkki (2022)
    Background: Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce.Methods: In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors.Results: Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27-4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91-1.00). Limitations: Moderate sample size and follow-up duration.Conclusions: Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.
  • Marola, Niko; Miranda, Michele; Shanmugalingam, Nageswari (2016)
    The overarching goal of this paper is to link the notion of sets of finite perimeter (a concept associated with N (1,1)-spaces) and the theory of heat semigroups (a concept related to N (1,2)-spaces) in the setting of metric measure spaces whose measure is doubling and supports a 1-Poincar, inequality. We prove a characterization of sets of finite perimeter in terms of a short time behavior of the heat semigroup in such metric spaces. We also give a new characterization of BV functions in terms of a near-diagonal energy in this general setting.
  • Erkan, Erdogan Pekcan; Ströbel, Thomas; Dorfer, Christian; Sonntagbauer, Markus; Weinhäusel, Andreas; Saydam, Nurten; Saydam, Okay (2019)
    Meningiomas are primary central nervous system (CNS) tumors that originate from the arachnoid cells of the meninges. Recurrence occurs in higher grade meningiomas and a small subset of Grade I meningiomas with benign histology. Currently, there are no established circulating tumor markers which can be used for diagnostic and prognostic purposes in a non-invasive way for meningiomas. Here, we aimed to identify potential biomarkers of meningioma in patient sera. For this purpose, we collected preoperative (n = 30) serum samples from the meningioma patients classified as Grade I (n = 23), Grade II (n = 4), or Grade III (n = 3). We used a high-throughput, multiplex immunoassay cancer panel comprising of 92 cancer-related protein biomarkers to explore the serum protein profiles of meningioma patients. We detected 14 differentially expressed proteins in the sera of the Grade I meningioma patients in comparison to the age- and gender-matched control subjects (n = 12). Compared to the control group, Grade I meningioma patients showed increased serum levels of amphiregulin (AREG), CCL24, CD69, prolactin, EGF, HB-EGF, caspase-3, and decreased levels of VEGFD, TGF-α, E-Selectin, BAFF, IL-12, CCL9, and GH. For validation studies, we utilized an independent set of meningioma tumor tissue samples (Grade I, n = 20; Grade II, n = 10; Grade III, n = 6), and found that the expressions of amphiregulin and Caspase3 are significantly increased in all grades of meningiomas either at the transcriptional or protein level, respectively. In contrast, the gene expression of VEGF-D was significantly lower in Grade I meningioma tissue samples. Taken together, our study identifies a meningioma-specific protein signature in blood circulation of meningioma patients and highlights the importance of equilibrium between tumor-promoting factors and anti-tumor immunity.
  • Pulkka, Olli-Pekka; Mpindi, John-Patrick; Tynninen, Olli; Nilsson, Bengt; Kallioniemi, Olli; Sihto, Harri; Joensuu, Heikki (2018)
    The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
  • Alabi, Rasheed Omobolaji; Mäkitie, Antti A.; Pirinen, Matti; Elmusrati, Mohammed; Leivo, Ilmo; Almangush, Alhadi (2021)
    Background: The prediction of overall survival in tongue cancer is important for planning of personalized care and patient counselling. Objectives: This study compares the performance of a nomogram with a machine learning model to predict overall survival in tongue cancer. The nomogram and machine learning model were built using a large data set from the Surveillance, Epidemiology, and End Results (SEER) program database. The comparison is necessary to provide the clinicians with a comprehensive, practical, and most accurate assistive system to predict overall survival of this patient population. Methods: The data set used included the records of 7596 tongue cancer patients. The considered machine learning algorithms were logistic regression, support vector machine, Bayes point machine, boosted decision tree, decision forest, and decision jungle. These algorithms were mainly evaluated in terms of the areas under the receiver operating characteristic (ROC) curve (AUC) and accuracy values. The performance of the algorithm that produced the best result was compared with a nomogram to predict overall survival in tongue cancer patients. Results: The boosted decision-tree algorithm outperformed other algorithms. When compared with a nomogram using external validation data, the boosted decision tree produced an accuracy of 88.7% while the nomogram showed an accuracy of 60.4%. In addition, it was found that age of patient, T stage, radiotherapy, and the surgical resection were the most prominent features with significant influence on the machine learning model's performance to predict overall survival. Conclusion: The machine learning model provides more personalized and reliable prognostic information of tongue cancer than the nomogram. However, the level of transparency offered by the nomogram in estimating patients' outcomes seems more confident and strengthened the principle of shared decision making between the patient and clinician. Therefore, a combination of a nomogram - machine learning (NomoML) predictive model may help to improve care, provides information to patients, and facilitates the clinicians in making tongue cancer management-related decisions.
  • Int Bilateral-Pheochromocytoma-Reg; Neumann, Hartmut P. H.; Tsoy, Uliana; Bancos, Irina; Schalin-Jäntti, Camilla; Eng, Charis (2019)
    IMPORTANCE Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. OBJECTIVE To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. EXPOSURES Total or cortical-sparing adrenalectomy. MAIN OUTCOMES AND MEASURES Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. RESULTS Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutationswere detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survivalwas associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. CONCLUSIONS AND RELEVANCE Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.
  • Saarinen, Irena; Mirtti, Tuomas; Seikkula, Heikki; Bostrom, Peter J.; Taimen, Pekka (2015)
    Background Prostate cancer (PCa) is the most common cancer among men in western countries. While active surveillance is increasingly utilized, the majority of patients are currently treated with radical prostatectomy. In order to avoid over-treatment, there is an indisputable need for reliable biomarkers to identify the potentially aggressive and lethal cases. Nuclear intermediate filament proteins called lamins play a role in chromatin organization, gene expression and cell stiffness. The expression of lamin A is associated with poor outcome in colorectal cancer but to date the prognostic value of the lamins has not been tested in other solid tumors. Methods We studied the expression of different lamins with immunohistochemistry in a tissue microarray material of 501 PCa patients undergoing radical prostatectomy and lymph node dissection. Patients were divided into two staining categories (low and high expression). The correlation of lamin expression with clinicopathological variables was tested and the association of lamin status with biochemical recurrence (BCR) and disease specific survival (DSS) was further analyzed. Results Low expression of lamin A associated with lymph node positivity (p Conclusions These results suggest differential roles for lamins in PCa progression. Reduced amounts of lamin A/C and B2 increase risk for lymph node metastasis and disease specific death possibly through increased nuclear deformability while high expression of lamin B1 predicts disease recurrence.
  • Fleischer, Thomas; Klajic, Jovana; Aure, Miriam Ragle; Louhimo, Riku; Pladsen, Arne V.; Ottestad, Lars; Touleimat, Nizar; Laakso, Marko; Halvorsen, Ann Rita; Alnaes, Grethe I. Grenaker; Riis, Margit L. H.; Helland, Aslaug; Hautaniemi, Sampsa; Lonning, Per Eystein; Naume, Bjorn; Borresen-Dale, Anne-Lise; Tost, Joerg; Kristensen, Vessela N. (2017)
    Breast cancer patients with Luminal A disease generally have a good prognosis, but among this patient group are patients with good prognosis that are currently overtreated with adjuvant chemotherapy, and also patients that have a bad prognosis and should be given more aggressive treatment. There is no available method for subclassification of this patient group. Here we present a DNA methylation signature (SAM40) that segregates Luminal A patients based on prognosis, and identify one good prognosis group and one bad prognosis group. The prognostic impact of SAM40 was validated in four independent patient cohorts. Being able to subdivide the Luminal A patients may give the two-sided benefit of identifying one subgroup that may benefit from a more aggressive treatment than what is given today, and importantly, identifying a subgroup that may benefit from less treatment.
  • Zhou, Wenjing; Sollie, Thomas; Tot, Tibor; Blomqvist, Carl; Abdsaleh, Shahin; Liljegren, Göran; Warnberg, Fredrik (2017)
    Casting-type calcifications and a histopathological picture with cancer-filled duct-like structures have been presented as breast cancer with neoductgenesis. We correlated mammographic features and histopathological neoductgenesis with prognosis in a DCIS cohort with long follow-up. Mammographic features were classified into seven groups according to Tabar. Histopathological neoductgenesis was defined by concentration of ducts, lymphocyte infiltration, and periductal fibrosis. Endpoints were ipsilateral (IBE) in situ and invasive events. Casting-type calcifications and neoductgenesis were both related to high nuclear grade, ER-and PR-negativity, and HER2 overexpression but not to each other. Casting-type calcifications and neoductgenesis were both related to a nonsignificant lower risk of invasive IBE, HR 0.38 (0.13-1.08) and 0.82 (0.29-2.27), respectively, and the HR of an in situ IBE was 0.90 (0.41-1.95) and 1.60 (0.75-3.39), respectively. Casting-type calcifications could not be related to a worse prognosis in DCIS. We cannot explain why a more aggressive phenotype of DCIS did not correspond to a worse prognosis. Further studies on how the progression from in situ to invasive carcinoma is driven are needed.
  • Joensuu, Heikki; Wardelmann, Eva; Sihto, Harri; Eriksson, Mikael; Hall, Kirsten Sundby; Reichardt, Annette; Hartmann, Joerg T.; Pink, Daniel; Cameron, Silke; Hohenberger, Peter; Al-Batran, Salah-Eddin; Schlemmer, Marcus; Bauer, Sebastian; Nilsson, Bengt; Kallio, Raija; Junnila, Jouni; Vehtari, Aki; Reichardt, Peter (2017)
    IMPORTANCE Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations. OBJECTIVE To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. DESIGN, SETTING, AND PARTICIPANTS This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES The main outcome was RFS. Mutations were grouped by the gene and exon. KIT exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558. RESULTS Of the 341 patients (175 men and 166women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a KIT mutation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs thatwere wild type for these genes. PDGFRA mutations and KIT exon 11 insertion or duplication mutations were associated with favorable RFS, whereas KIT exon 9 mutations were associated with unfavorable outcome. Patients with KIT exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%; P CONCLUSIONS AND RELEVANCE Patients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558.
  • Peltonen, Reetta; Gramkow, Mathias H.; Dehlendorff, Christian; Osterlund, Pia J.; Johansen, Julia S.; Isoniemi, Helena (2020)
    Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2–5 elevated biomarkers were at an increased risk of relapse compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1–1.72) or postoperatively (HR 1.54, 95% CI 1.23–1.92). Patients with 2–5 elevated biomarkers were also at an increased risk of death compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39–2.24) or postoperatively (HR 1.83, 95% CI 1.44–2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.
  • Mohamed, Hesham; Haglund, Caj; Jouhi, Lauri; Atula, Timo; Hagström, Jaana; Mäkitie, Antti (2020)
    Oropharyngeal squamous cell carcinoma (OPSCC) is subclassified by the World Health Organization into two different entities: human papillomavirus (HPV)-positive and HPV-negative tumors. HPV infection promotes the epithelial-to-mesenchymal transition (EMT) and transformation of keratinocyte stem cells into cancer stem cells. EMT is a crucial process in the carcinogenesis of epithelial-derived malignancies, and we aimed to study the role of its markers in OPSCC. This study consists of 202 consecutive OPSCC patients diagnosed and treated with curative intent. We examined E-cadherin, beta-catenin, and vimentin expression using immunohistochemistry and compared these with tumor and patient characteristics and treatment outcome. We found that the cell-membranous expression of beta-catenin was stronger in HPV-positive than in HPV-negative tumors, and it was stronger in the presence of regional metastasis. The stromal vimentin expression was stronger among HPV-positive tumors. A high E-cadherin expression was associated with tumor grade. No relationship between these markers and survival emerged. In conclusion, beta-catenin and vimentin seem to play different roles in OPSCC: the former in the tumor tissue itself, and the latter in the tumor stroma. HPV infection may exploit the beta-catenin and vimentin pathways in carcinogenic process. More, beta-catenin may serve as a marker for the occurrence of regional metastasis:
  • EXTEND Clinical Study Grp (2018)
    Background Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin. Methods In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals. Patients were randomly assigned (1: 1) using an interactive web response system to receive extended-pulsed fidaxomicin (200 mg oral tablets, twice daily on days 1-5, then once daily on alternate days on days 7-25) or vancomycin (125 mg oral capsules, four times daily on days 1-10), stratified by baseline C difficile infection severity, cancer presence, age (>= 75 years vs Findings Between Nov 6, 2014, and May 5, 2016, 364 patients were enrolled and randomly assigned to receive extended-pulsed fidaxomicin or vancomycin. 362 patients received at least one dose of study medication (181 in each group). 124 (70%) of 177 patients in the modified full analysis set receiving extended-pulsed fidaxomicin achieved sustained clinical cure 30 days after end of treatment, compared with 106 (59%) of 179 patients receiving vancomycin (difference 11% [95% CI 1.0-20.7], p=0.030; odds ratio 1.62 [95% CI 1.04-2.54]). Incidence of treatment-emergent adverse events did not differ between extended-pulsed fidaxomicin (121 [67%] of 181) and vancomycin (128 [71%] of 181) treatment arms. One death in the vancomycin arm was considered by the investigator to be related to study drug. Interpretation Extended-pulsed fidaxomicin was superior to standard-dose vancomycin for sustained cure of C difficile infection, and, to our knowledge, extended-pulsed fidaxomicin recurrence rates in this study are the lowest observed in a randomised clinical trial of antibiotic treatment for C difficile infection.